A method of asymmetrically reducing the carbonyl group of a carbonyl compound using a microorganism or an enzyme is known as one of the methods for producing optically active alcohols useful as starting materials or intermediates for the synthesis of pharmaceuticals or agricultural chemicals. Asymmetric enzymes reducing carbonyl compounds (hereinafter, carbonyl reductases) are useful in the production of various optically active alcohols.
The asymmetric reduction reactions using carbonyl reductases may suffer from deactivation of the enzyme or inhibition of the enzymatic reaction due to the presence of the substrate or generated products, the acid or alkali used in pH adjustment, the surfactant or organic solvent added to improve the properties of the reaction mixture, or the like. Accordingly, carbonyl reductases capable of avoiding the deactivation of the enzyme or inhibition of the enzyme reaction by the organic solvent or the like provide shortening of the reaction time and improvement in the reaction yield, and are thus more useful in the industrial production of optically active alcohols.
For example, there have been attempts to acquire organic solvent resistance by random mutation, and Patent Literature 1 and Non Patent Literature 1 describe reductases that are resistant to 2-propanol or dimethyl sulfoxide.
However, there are only a few enzymes resistant to dimethylformamide, an industrially highly useful organic solvent, and at present no reductase having practical levels of dimethylformamide resistance has been reported.